The primary goal of this project is to determine the role of variation in HIV sequences in causing the various clinical manifestations seen in AIDS. In vivo env sequence analysis of viruses associated with dementia suggested that unique viral strains may be responsible for the occurrence of HIV dementia. In contrast, other analyses indicated that dementia was not associated with higher levels of viral DNA. Viruses containing large regions of envelope genes derived from demented or nondemented patients were generated by molecular cloning and were used to infect human macrophages in cultures. The supernatant fluids from such cultures were tested for toxicity on human neuron cultures, and more toxicity was produced by supernatants from cultures exposed to viruses containing sequences from demented patients. These results support the possibility that HIV strains differ in their ability to cause damage to neurons in cultures and in patients. - HIV, brain disease, macrophages, microglia